Clinical and laboratory endeavors involve three major areas of immunodermatology. The first deals with studies of patients with various forms of vesiculobullous diseases. We have not only provided detailed clinicoimmunopathological correlations of several heretofore poorly defined diseases, i.e., dermatitis herpetiformis, acquired epidermolysis bullosa and herpes gestationis but we have characterized the antigens to which the antibodies in some of these diseases bind, i.e., pemphigus and pemphigoid antigens. These studies are closely linked to my second major area of interest which is to provide an understanding of and to chemically characterize ultrastructurally-defined components of the epidermal basement membrane and to deterine the function of each of these. We have demonstrated that epidermal cells synthesize both the skin specific pemphigoid antigen and the ubiquitous laminin, both of which are localized to the lamina lucida of the basement membrane zone. We have also recently described, by using monoclonal antibodies, another stratified squamous epithelial specific basement membrane protein which is defined by the KF-1 antibody. This basement membrane zone antigen is a noncollagenous component of the lamina densa which was previously thought to contain only type IV procollagen. In recent studies we have found that the antigen defined by KF-1 is specifically absent or markedly diminished in the dystrophic forms of epidermolysis bullosa which is a severely mutilating disease characterized by marked skin fragility and blisters. My third and major area of interest is the role of the epidermis as an immunological tissue. We have, using mouse, human and guinea pig skin, demonstrated that within mormal epidermis Langerhans cells are the only cells which 1) synthesize and express Ia antigens, 2) can present both soluble antigens and haptens to sensitized T cells, 3) are capable of allogeneic T cell stimulation in a mixed epidermal-lymphocyte proliferation system, 4) can induce hapten and allogeneic cytotoxic T lymphocytes in vitro, and 5) are of a mesenchymal origin. We have also demonstrated that keratinocytes produce an Interleukin 1-like cytokine which may serve as a second signal in generating T cell responses.